Protein kinase C as a modulator of response amplification in vascular smooth muscle.
The amplification of alpha-adrenoceptor-mediated vasoconstriction by angiotensin II was studied in femoral artery rings from rabbits. Threshold concentrations of angiotensin II (0.1 nM) increased the maximal response to clonidine to 139 +/- 8% of control and produced a 3.2-fold increase in sensitivity. These effects of angiotensin II were reversed when tissues were pretreated with staurosporine (50 nM), an inhibitor of protein kinase C. The amplification of the alpha-adrenoceptor-mediated vasoconstrictor effects of thrombin and norepinephrine by angiotensin II were also reversed by pretreatment with staurosporine. Angiotensin II induced a response amplification in vascular smooth muscle known to be a nonspecific phenomenon, implying postreceptor interaction at intracellular transducer systems. Our findings suggest that upon activation of protein kinase C by angiotensin II, arterial responses to alpha-adrenoceptor agonists are amplified. This provides for nonspecific changes in vascular sensitivity by tonic alterations in postsynaptic modulation by enzyme systems known to regulate Ca2(+)-dependent phenomena, e.g. those related to vascular excitation-contraction mechanisms.
Laher
I
I
Department of Pharmacology, University of Vermont, College of Medicine, Burlington.
Thompson
L P
LP
Gagne
L
L
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004056:Differential Threshold; D004347:Drug Interactions; D005263:Femoral Artery / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011817:Rabbits; D019311:Staurosporine; D013917:Thrombin / Q000494:pharmacology; D014661:Vasoconstriction
D000470:Alkaloids; D000804:Angiotensin II; D011493:Protein Kinase C; D013917:Thrombin; D019311:Staurosporine; D003000:Clonidine; D009638:Norepinephrine